Pathobiology of Novel Treatments for IPF

Question 1

What are some symptoms experienced by patients with IPF

Answer 1

Breathlessness

Cough

Question 2

What are some investigations to diagnose/manage IPF

Answer 2

• Respiratory Exam
• HRCT
• Bronchoscopy
• BAL
• Biopsy

Question 3

What are some radiographic features seen in HRCT of IPF patients

Answer 3

• Heterogeneous lung
  
  • UIP (Usual Interstitial Pneumonia)
• Honeycombing
  
  • Effects peripheral bases of lung (subpleural)
• Traction bronchiectasis

Question 4

Give an overview of the wound healing process

Answer 4

• Damaged epithelium - coagulation occurs and fibrin clots
• Inflammation with clearanc of pathogens by macrophage and neutrophils
• TGF-B and PDGF activate fibroblasts
• Myofibroblasts deposit collagen type I and III
• Scaffolding for tissue healing
• Apoptosis of fibroblasts and resorption of ECM when healed

Question 5

What are three factors which contribute to the pathology of IPF

Answer 5

• Genetic predisposition
• Alveolar Injury
• Senscence

Question 6

What are some genetic factors/polymorphisms that predispose IPF

Answer 6

• MUC5B
  
  • Host Defense
• TERT/TERC
  
  • Cell ageing/senescence
• Integrin
  
  • Cellular integrity

Question 7

What are some environmental factors that lead to IPF

Answer 7

• Repetitive Alveolar Injury
  
  • Occuation (smoke, dust)
  • Infection (EBV)
  • Hiatus Hernia/GORD (microaspirations)

data to suggest IPF has higher bacterial load compared to healthy and COPD controls Molyneaux et al AJRCCM 2014

Question 8

How does senescence lead to IPF

Answer 8

Alveolar injury leads to mor proliferation and division of epithelial cells

Telomere attrition

Stemm cell exhaustion

Senescence and inability to replace damage tissue

Question 9

Outline the general pathophysiology of IPF

Answer 9

Maher et al Clinics Chest Med 2012

Question 10

The average patient is _____ in their mid-late 60s, former _____ and will have worked in _____/_____ environment. There are different phenotypes of disease progression. 1:20 have acute _____ which leads to _____. These exacerbations are _____ in terms of lung function.

Answer 10

The average patient is male in their mid-late 60s, former smoker and will have worked in smoky/dustyenvironment. There are different phenotypes of disease progression. 1:20 have acute exacerbations which leads to ARDS. These exacerbations are irreversible in terms of lung function.

Question 11

In terms of exacerbations, how are IPf and asthma/COPD exacerbations different

Answer 11

BOth caused by infections

IPF - diffuse alveolar damage -> ARDS on top of their fibrosed lung

Asthma/COPD - inflmmation with mucus hypersecretion

Question 12

What are the current treatments for IPF

Answer 12

• Lung Transplantation
• Pirfenidone
• Nintedanib

Question 13

With the pathophysiology of IPF in mnd, what kind of treatments are being studied for IPF

Answer 13

• Anti-Oxidants
  
  • Prevent Injury
• Coagulation inhibitors
• Epithelial stimulation for repair
• Fibroblast inhibition
• Endothelial inhibition

Maher TM Clinics Chest Med 2012

Question 14

How are we looking to treat IPF in the futurs?

Answer 14

• Combination therapy
  
  • IPF is multiple pathway disesae
• Personalised therapy

Question 15

What are some complications of IPF

Answer 15

• Respiratory Failure
  
  • Treat with O2
• Pulmonary HTN
• Lung Cancer
• Infection
• Acute Exacerbations -> ARDS